Current estimates indicate that about a third of the world's population is infected with M. tuberculosis, 8.7 million individuals develop the disease annually, and almost 2 million die each year from the disease. Tuberculosis control programs are threatened by the emergence and transmission of multidrug resistant (MDR) and extensively drug resistant (XDR) tuberculosis since the treatment of these cases is more complex, more costly, and frequently less successful than the treatment of drug sensitive strains. The goals of this proposed Program Project are to conduct a series of linked interdisciplinary research projects focused on the emergence and transmission of multidrug and extensively drug resistant tuberculosis and to support these projects through the development of a central core for administration and leadership, database management and a central M. tuberculosis isolate archive. Linked research projects include: a cohort study of host and microbial factors associated with the emergence and transmission of drug sensitive and resistant TB in Lima, Peru; a study designed to characterize M. tuberculosis strain diversity and its contribution to the emergence and spread of MDR; and a study to use epidemic and individual predictive models to support public health policy and clinical decision making for MDR and XDR tuberculosis. [unreadable] [unreadable] PROJECT 1: Host and microbial risk factors for drug-sensitive and -resistant tuberculosis Becerra, M [unreadable] [unreadable] Description (provided by applicant): M. tuberculosis is a highly successful pathogen that infects over eight million people per year and leads to over 2 million deaths. One third of the world's population is believed to be infected with this organism, but only a small minority of those infected will go on to develop active disease. Although some risk factors for disease progression have been described, host and microbial mechanisms that lead to increased susceptibility are poorly understood. The identification of factors associated with the transmission and progression of drug sensitive and resistant tuberculosis may provide targets for focused clinical and public health interventions. Such interventions will be of particular importance for the control of drug resistant tuberculosis, since current control measures focus on the effective treatment of infectious cases. The long term goals are to elucidate factors involved in the emergence and transmission of multidrug (MDR) and extensively drug resistant (XDR) tuberculosis and to develop and implement interventions that target these factors in order to reduce tuberculosis progression and transmission. The specific aims of this project are to identify host, microbial and environmental risk factors for the development of drug sensitive (DS) and MDR tuberculosis and to archive strains characterized on the basis of their epidemiologic and clinical behavior so that they can be used in basic research on strain diversity and its contribution to MDR. We will also establish a comprehensive database which will allow real-time surveillance and be used for epidemic modeling and individual prediction models that will assist decision making regarding the treatment of drug resistant tuberculosis. [unreadable] [unreadable] [unreadable]